Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway.

Abstract

Clinical trials have shown that angiotensin II receptor blockers reduce the new onset of diabetes in hypertensives; however, the underlying mechanisms remain unknown. We investigated the effects of telmisartan on peroxisome proliferator activated receptor γ (PPAR-δ) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in cultured myotubes, as well as on the running endurance of wild-type and PPAR-δ-deficient mice. Administration of telmisartan up-regulated levels of PPAR-δ and phospho-AMPKα in cultured myotubes. However, PPAR-δ gene deficiency completely abolished the telmisartan effect on phospho-AMPKαin vitro. Chronic administration of telmisartan remarkably prevented weight gain, enhanced running endurance and post-exercise oxygen consumption, and increased slow-twitch skeletal muscle fibres in wild-type mice, but these effects were absent in PPAR-δ-deficient mice. The mechanism is involved in PPAR-δ-mediated stimulation of the AMPK pathway. Compared to the control mice, phospho-AMPKα level in skeletal muscle was up-regulated in mice treated with telmisartan. In contrast, phospho-AMPKα expression in skeletal muscle was unchanged in PPAR-δ-deficient mice treated with telmisartan. These findings highlight the ability of telmisartan to improve skeletal muscle function, and they implicate PPAR-δ as a potential therapeutic target for the prevention of type 2 diabetes.

• Authors: Xiaoli Feng, Zhidan Luo, Liqun Ma, Shuangtao Ma, Dachun Yang, Zhigang Zhao, Zhencheng Yan, Hongbo He, Tingbing Cao, Daoyan Liu, Zhiming Zhu
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 15 Issue 7 Pg. 1572-81 (Jul 2011) ISSN: 1582-4934 [Electronic] England
• PMID: 20477906 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Benzoates
• PPAR delta
• Adenylate Kinase
• Telmisartan

Topics

• Adenylate Kinase (metabolism)
• Angiotensin II Type 1 Receptor Blockers (metabolism, therapeutic use)
• Animals
• Benzimidazoles (metabolism, therapeutic use)
• Benzoates (metabolism, therapeutic use)
• Cells, Cultured
• Diabetes Mellitus, Type 2 (drug therapy)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Muscle, Skeletal (cytology, physiology)
• Oxygen Consumption (physiology)
• PPAR delta (genetics, metabolism)
• Physical Endurance (physiology)
• Running (physiology)
• Telmisartan